Characterizing the Efficacy of Fermented Wheat Germ Extract Against Ovarian Cancer and Defining the Genomic Basis of Its Activity
ABSTRACT Most women with advanced-stage epithelial ovarian cancer (OVCA) ultimately develop chemoresistant recurrent disease. Therefore, a great need to develop new, more active, and less toxic agents and/or to optimize the efficacy of existing agents exists.
In this study, we investigated the activity of Avemar, a natural, nontoxic, fermented wheat germ extract (FWGE), against a range of OVCA cell lines, both alone and in combination with cisplatin chemotherapy and delineated the molecular signaling pathways that underlie FWGE activity at a genome-wide level.
We found that FWGE exhibited significant antiproliferative effects against 12 human OVCA cell lines and potentiated cisplatin-induced apoptosis. Pearson correlation of FWGE sensitivity and gene expression data identified 2142 genes (false discovery rate < 0.2) representing 27 biologic pathways (P < 0.05) to be significantly associated with FWGE sensitivity. A parallel analysis of genomic data for 59 human cancer cell lines matched to chemosensitivity data for 2,6-dimethoxy-p-benzoquinone, a proposed active component of FWGE, identified representation of 13 pathways common to both FWGE and 2,6-dimethoxy-p-benzoquinone sensitivity.
Our findings confirm the value of FWGE as a natural product with anticancer properties that may also enhance the activity of existing therapeutic agents. Furthermore, our findings provide substantial insights into the molecular basis of FWGE's effect on human cancer cells. RESEARCH HIGHLIGHTS:
Full-textDOI: · Available from: Robert Wenham, Jul 07, 2014
[Show abstract] [Hide abstract]
ABSTRACT: This study aimed to evaluate the anticarcinogenic activities of aqueous extract of fermented wheat germ with Lactobacillus plantarum dy-1 (LFWGE). The anticarcinogenic activities, including antiproliferative effects and the induction of apoptosis, were studied in human HT-29 colon cancer cells. The 2, 6-dimethoxybenzoquinone and total phenols contents in LFWGE were determined by HPLC and the Folin-Ciocalteu method. In addition, some functional proteins were separated and purified by gel filtration chromatography. Twenty-one proteins were identified by LC-MS-MS. The sugars isolated from LFWGE did not possess any anticarcinogenic activity. The results of an MTT assay showed high antiproliferative effects of LFWGE. In addition, LFWGE attenuated the progression from the G0-G1 to the G2-M phase of the cell cycle and LFWGE-induced cell apoptosis was associated with the activation of caspase-3. LFWGE and its major bioactive ingredients inhibited the proliferation of HT-29 cells via apoptosis and thus may be a potential anticarcinogenic agent.Journal of Agricultural and Food Chemistry 02/2015; 63(9). DOI:10.1021/acs.jafc.5b00041 · 3.11 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death worldwide. Due to the difficulties of early diagnosis, curative treatments are not available for most patients. Palliative treatments such as chemotherapy are often associated with low response rate, strong adverse effects and limited clinical benefits for patients. The alternative approaches such as fermented wheat germ extract (FWGE) with anti-tumor efficacy may provide improvements in the clinical outcome of current therapy for HCC. This study aimed to clarify antitumor efficacy of FWGE and the combination drug effect of FWGE with chemotherapeutic agents, cisplatin and 5-fluorouracil (5-Fu) in human HCC cells, HepG2, Hep3B, and HepJ5. The present study indicated that FWGE exhibited potential to suppress HepG2, Hep3B, and HepJ5 cells, with the half maximal inhibitory concentrations (IC50) of FWGE were 0.494, 0.371 and 1.524 mg/mL, respectively. FWGE also induced Poly (Adenosine diphosphate ribose) polymerase (PARP) associated cell death in Hep3B cells. Moreover, the FWGE treatment further enhanced the cytotoxicity of cisplatin in all tested HCC cells, and cytotoxicity of 5-Fu in a synergistic manner in HepJ5 cells. Collectively, the results identified the anti-tumor efficacy of FWGE in HCC cells and suggested that FWGE can be used as a supplement to effectively improve the tumor suppression efficiency of cisplatin and 5-Fu in HCC cells.Evidence-based Complementary and Alternative Medicine 12/2013; 2013:121725. DOI:10.1155/2013/121725 · 2.18 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: In the last decade, several studies described the promising cytotoxic activity of fermented wheat germ towards cancer cell lines and during in vivo clinical trials. Recent data suggested that the antiproliferative, antimetastatic and immunological effects of this preparation are mainly attributed to quinones. This study aimed at exploiting the potential of sourdough lactic acid bacteria fermentation to release 2-methoxy benzoquinone, and 2,6-dimethoxybenzoquinone, which are naturally present in wheat germ as glycosylated and non-physiologically active form. Preliminarily, forty strains of lactic acid bacteria, previously isolated from wheat germ, were in vitro screened based on beta-glucosidase activity. Lactobacillus plantarum LB1 and Lactobacillus rossiae LB5 were selected based on the highest enzyme activity and on technology features. These strains were used in combination to ferment wheat germ. Raw wheat germ, without bacterial inoculum, was subjected to the same incubation and used as the control. The sourdough fermented wheat germ was characterized based on microbiological, physico-chemical and biochemical features. During incubation, the release of the non-glycosylated and physiologically active 2-methoxy benzoquinone, and 2,6-dimethoxybenzoquinone was almost completed during 24 h. Compared to the control, the concentration of the above bioactive compounds increased almost 4 and 6-folds. Both raw wheat germ (control) and sourdough fermented wheat germ were ex vivo assayed for the anti-proliferative activity towards various cell lines of germ cell tumor, colon carcinoma and ovarian carcinoma. While no effect was found for the raw wheat germ, the sourdough fermented preparation markedly and variously affected the human tumor cell lines. The values of IC50 ranged from 0.105 +/- 0.005 to 0.556 +/- 0.071 mg/ml, with a median value of IC50 of 0.302 mg/ml. These results are comparable to those found for other well-known pharmaceutical preparations, and may disclose the use of the sourdough fermented wheat germ as an ingredient, nutritional supplement and/or anticancer drug.Microbial Cell Factories 11/2013; 12(1):105. DOI:10.1186/1475-2859-12-105 · 4.25 Impact Factor